U.S. patent application number 10/380706 was filed with the patent office on 2004-12-09 for method for the purification of a-hydroxy acids on an industrial scale.
Invention is credited to van Krieken, Jan.
Application Number | 20040249206 10/380706 |
Document ID | / |
Family ID | 19772099 |
Filed Date | 2004-12-09 |
United States Patent
Application |
20040249206 |
Kind Code |
A1 |
van Krieken, Jan |
December 9, 2004 |
Method for the purification of a-hydroxy acids on an industrial
scale
Abstract
The present invention relates to a method for the purification
of an .alpha.-hydroxy acid on an industrial scale, in which an
.alpha.-hydroxy acid with a colour (fresh) of not more than 10,000
APHA units is subjected to (a) a crystallization step followed by
(b) a distillation step.
Inventors: |
van Krieken, Jan;
(Gorinchen, NL) |
Correspondence
Address: |
PATENT ADMINSTRATOR
KATTEN MUCHIN ZAVIS ROSENMAN
525 WEST MONROE STREET
SUITE 1600
CHICAGO
IL
60661-3693
US
|
Family ID: |
19772099 |
Appl. No.: |
10/380706 |
Filed: |
January 12, 2004 |
PCT Filed: |
September 14, 2001 |
PCT NO: |
PCT/NL01/00682 |
Current U.S.
Class: |
562/589 |
Current CPC
Class: |
C07C 59/08 20130101;
C07C 59/08 20130101; C07C 59/06 20130101; C07C 59/06 20130101; C07C
51/43 20130101; C07C 51/44 20130101; C07C 51/43 20130101; C07C
51/44 20130101; C07C 51/44 20130101; C07C 51/43 20130101 |
Class at
Publication: |
562/589 |
International
Class: |
C07C 059/08 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 15, 2000 |
NL |
1016203 |
Claims
1. Method for the purification of an .alpha.-hydroxy acid on an
industrial scale, in which an .alpha.-hydroxy acid with a colour
(fresh) of not more than 10,000 APHA units is subjected to (a) a
crystallization step followed by (b) a distillation step.
2. Method according to claim 1, in which the .alpha.-hydroxy acid
is lactic acid or glycolic acid.
3. Method according to claim 2, in which the .alpha.-hydroxy acid
is lactic acid.
4. Method according to one of the preceding claims, in which step
(a) comprises two crystallization steps.
5. Method according to claim 4, in which the crystallization steps
are carried out in one device.
6. Method according to one of the preceding claims, in which step
(a) is carried out in a cooling crystallization device, a melting
crystallization device, an evaporative crystallization device an/or
an adiabatic crystallization device.
7. Method according to one of the preceding claims, in which the
product stream from step (a) is separated into a mother liquor and
.alpha.-hydroxy acid crystals by means of solid-liquid separation,
preferably centrifugation or with the aid of one or more washing
columns.
8. Method according to one of the preceding claims, in which step
(b) is carried out in one or more falling-film evaporators and/or
thin-film evaporators and/or smeared film evaporators.
9. Method according to one of the preceding claims, in which step
(b) is carried out in a short-path distiller.
Description
[0001] The present invention relates to a method for the
purification of .alpha.-hydroxy acids, in particular lactic acid or
glycolic acid, on an industrial scale, as well as to products of
the utmost chiral purity which can be obtained by this method, and
to applications thereof.
[0002] Lactic acid is usually marketed as a dilute or concentrated
solution, because lactic acid has a strong tendency to form
intermolecular esters (dimeric and polymeric lactic acid). In
addition, lactic acid (even very pure lactic acid) is strongly
hygroscopic. The purification of lactic acid (the racemic mixture
and in particular the enantiomers of lactic acid) on an industrial
scale is a complicated and difficult process according to the prior
art.
[0003] It is known how to produce lactic acid, or
2-hydroxypropionic acid, in a fermentative manner. In general the
fermentative production of lactic acid includes first of all a
fermentation step in which a carbohydrate-containing substrate such
as glucose or sucrose is converted to lactic acid by a suitable
microorganism. Known microorganisms producing (S)-lactic acid are
various bacteria of the genus Lactobacillus, such as Lactobacillus
casei for example. In addition microorganisms are also known which
produce R-lactic acid selectively. The aqueous fermentation product
is then processed in order to obtain lactic acid. The usual
industrial processing path generally consists of separation of the
biomass followed by acidification, purification and
concentration.
[0004] In the case of (S)-lactic acid the lactic acid so obtained
is sufficiently pure to be processed in foods for human
consumption. (S)- or (R)-lactic acid which is ultimately obtained
by this usual method can be 98% enantiomerically pure or even
higher (i.e. 98% or more of the lactic acid present consists of the
(S) or (R) enantiomer). The product still contains residual sugars,
however. The product is also yellow in colour and on heating this
becomes brown to black through decomposition of impurities.
Moreover, in the case of S-lactic acid, the organoleptic properties
often leave something to be desired. The lactic acid enantiomer is
thus moderately suitable for application in foods, but on the whole
not suitable for pharmaceutical applications and for synthesis of
chiral compounds.
[0005] The purity of the product can be increased by esterification
followed by hydrolysis, so that it is suitable for pharmaceutical
applications. As a result of this esterification/hydrolysis,
however, the enantiomeric purity decreases and the lactic acid
still contains a small amount of the alcohol which has been used in
the esterification. Examples of other methods for the purification
of lactic acid include subjecting aqueous solutions of lactic acid
to one or more extraction, (steam) distillation and/or evaporation
steps, electrodialysis steps and crystallizations (see for example
Ullmans Encyklopdie der Technischon Chemie, Verlag Chemie GmbH,
Weinheim, fourth edition, Part 17, pages 1-7 (1979); H. Benninga,
"History of Lactic Acid Making", Kluwer Academic Publishers,
Dordrecht--Boston--London (1990); C. H. Holten, "Lactic Acid;
Properties and Chemistry of Lactic Acid and Derivatives", Verlag
Chemie GmbH, Weinheim (1971); The Merck Index, Merck & Co.,
Inc., eleventh edition, page 842 (1989); Rommp Chemie Lexicon, G.
Thieme Verlag, Stuttgart and New York, ninth edition, Part 4, pages
2792-2893 (1991) and the Netherlands patent applications 103265 and
1013682.
[0006] In German Patent 593,657 (granted on Feb. 15, 1934) a
laboratory experiment is described in which an aqueous solution of
lactic acid, which contained an excess of the S component and
practically no lactic acid anhydride, was concentrated by means of
a thin-film evaporation technique, if necessary at reduced
pressure. The concentrated lactic acid solution was then rapidly
cooled, with formation of crystals. After that the crystals were
separated from the mother liquor, washed with ether and repeatedly
recrystallized from ethyl acetate or chloroform or a comparable
solvent until the crystals showed a sharp melting point of
53.degree. C. The chiral purity or the enantiomeric excess and the
colour are not reported.
[0007] In H. Borsook, H. M. Huffman, Y-P. Liu, J. Biol. Chem. 102,
449-460 (1993) a laboratory experiment is described in which an
aqueous mixture, which contained 50 per cent lactic acid with an
excess of S-lactic acid, 30 per cent lactic acid anhydride and
lactic acid dimer and 15 per cent water, was subjected to
fractional distillation at approximately 0.13 mbar and 105.degree.
C. The middle fraction was then distilled again and after that
cooled in an ice/salt bath with formation of a solid crystal mass.
It is reported that the distillation has to be performed with small
quantities, because with larger quantities there is a big loss of
product as a result of the long heating time. The solid crystal
mass was then recrystallized three times from an equal volume of
equal quantities of diethyl ether and diisopropyl ether, and the
crystals were isolated and dried at room temperature in a vacuum
drier. In this way it was possible to obtain (S)-lactic acid with a
melting point of 52.7-52.8.degree. C. which contained less than 0.1
per cent impurities such as water, lactic acid anhydride or lactic
acid dimer. The chiral purity or the enantiomeric excess and the
colour of S-lactic acid are not reported.
[0008] In L. B. Lockwood, D. E. Yoder, M. Zienry, Ann. N.Y. Acad.
Sci. 119, 854 (1965) the distillation and crystallization of lactic
acid on a laboratory scale is also described, the melting point of
the optically pure lactic acid obtained being 54.degree. C. The
colour is not reported.
[0009] In 1934 the crystallization of lactic acid was investigated
by Boehringer Ingelheim, but this method was not found to give good
results, owing to problems with the purification and further
treatment. After the Second World War, however, it turned out that
Boehringer Ingelheim was able to produce lactic acid for
pharmaceutical applications on a scale of about 12 to 15 tons per
month, with a yield of about 77 to 86 per cent. In this process an
aqueous solution of lactic acid was purified by means of steam
distillation at reduced pressure (about 13 mbar), followed by
crystallization at -25.degree. C., after which the crystals were
dissolved in water and the solution was treated with potassium
ferrocyanide (to remove heavy metals) and activated charcoal. The
chiral purity or the enantiomeric excess of other properties such
as colour and odour of the S-lactic acid so produced are not known
(see H. Benninga, "History of Lactic Acid Making", Kluwer Academic
Publishers, Dordrecht--Boston--London, pages 347-350 (1990)).
[0010] Crystalline (S)-lactic acid has been marketed by, for
example, Fluka and Sigma with purities of more than 99% (see for
example M. L. Buszko, E. R. Andrew, Mol. Phys. 76, 83-87 (1992) and
T. S. Ing, A. W. Yu, V. Nagaraja, N. A. Amin, S. Ayache, V. C.
Gandhi, J. T. Daugirdas, Int. J. Artif. Organs 17, 70-73 (1994)).
Crystalline S-lactic acid with a water content of less than 1 per
cent by weight is known from EP A 563,455 (see Example 1). The
crystal structure of lactic acid is described in A. Schouten, J. A.
Kanters, J. van Krieken, J. Mol. Struct. 323, 165-168 (1994).
[0011] Lactic acid can also be obtained in a synthetic manner. This
is known. The product of the synthetic production method, however,
is a racemic mixture which thus contains (S)-lactic acid and
(R)-lactic acid in equal quantities. It is true that the separate
enantiomers can be separated by means of known techniques, such as
diastereoisomer separation techniques, where one of the enantiomers
crystallizes out as a salt and this salt is then converted back to
the enantiomeric lactic acid, but the enantiomeric product finally
obtained will inevitably still contain significant quantities of
the other enantiomer.
[0012] In European Patent Application 552,255 it is reported that
glycolic acid of industrial quality can be crystallized by putting
a solution thereof in a freezer, giving rise to crystals which are
filtered off. It will be clear that such a method is unsuitable for
being carried out on an industrial scale. Such a method is also
applied in DE A 2,810,975.
[0013] In WO 00/56693 a method is described for the purification of
lactic acid on an industrial scale, the method involving: (a) the
distillation under reduced pressure of a concentrated lactic acid
solution with a total acid content of at least 95% by weight and a
monomeric lactic acid content of at least 80% by weight, calculated
in terms of the concentrated lactic acid solution, and with a ratio
of the lactic acid enantiomers not equal to 1, and (b) subjecting
the distilled lactic acid solution to a crystallization, with
formation of pure lactic acid, where the pure lactic acid has a
total acid content of at least 99% by weight, a monomeric lactic
acid content of at least 98% by weight, a chiral purity of 99% or
more, calculated in terms of the total quantity of pure lactic
acid, a colour of not more than 10 APHA units and an acceptable
odour.
[0014] Disadvantages of the method according to WO 00/56693 are
that the yield, although not low in relative terms, can be
improved, that the method requires a great deal of energy and that
a relatively large quantity of acid has to be distilled.
[0015] The present invention aims to solve these problems and
therefore relates to a method for the purification of an
.alpha.-hydroxy acid on an industrial scale (i.e. a scale of at
least 1000 tons per annum), in which an .alpha.-hydroxy acid with a
colour (fresh) of not more than 10,000 APHA units is subjected to
(a) a crystallization step followed by (b) a distillation step.
[0016] It will be clear to an expert that the method according to
the invention can comprise two or more crystallization steps and/or
two or more distillation steps. According to the invention,
however, it is preferable for only one crystallization step to be
performed, because otherwise the energy advantage would be
less.
[0017] Advantages of the method according to the invention are a
relatively low energy consumption. This is mainly due to the fact
that during the crystallization a relatively large amount of
impurities are removed and a product is obtained which contains
little water, generally less than 1% by weight, calculated in terms
of the whole product, so that this can be easily distilled (after
only melting). Moreover, the quantity of feed which has to be
distilled for an equal quantity of end product is much smaller.
[0018] An .alpha.-hydroxy acid means a carbonic acid which is
substituted with a hydroxy group on the .alpha. carbon atom. The
general formula of an .alpha.-hydroxy acid is therefore: 1
[0019] where R is a hydrogen atom, a C.sub.1-C.sub.5 alkyl group
(preferably a methyl group), a C.sub.6-C.sub.12 aryl group or a
heterocyclic cycloalkyl or -aryl group. The .alpha.-hydroxy acid
according to the invention is preferably lactic acid (R is methyl)
or glycolic acid (R is hydrogen) and is in particular lactic
acid.
[0020] The feed for the method is preferably characterized by a
colour (fresh) of not more than 7500 APHA and in particular of not
more than 5000 APHA, a total acid content of at least 70% by
weight, relative to the whole feed, and a free acid content of at
least 60% by weight, relative to the whole feed. If the
.alpha.-hydroxy acid is lactic acid, the feed preferably has a
total acid content of at least 80% by weight and a free acid
content of at least 70% by weight. The feed is further
characterized by a total nitrogen content of not more than 10,000
ppm, preferably not more than 5,000 ppm, and a total quantity of
residual sugars (predominantly polysaccharides) of not more than
20,000 ppm, preferably not more than 10,000 ppm, where all the
contents here indicated are relative to the whole feed. The chiral
purity of the feed, if applicable, is at least 90% and preferably
at least 95%.
[0021] Total acid content (TA) is the acid content after
saponification of intermolecular ester bonds with an excess base
and is determined by back titration with acid. The total acid
content thus gives the quantity of monomeric, dimeric and polymeric
lactic acid. The free acid content (FA) is determined by direct
titration with base, i.e. before saponification of the
intermolecular ester groups. The content of monomeric lactic acid
(MM) is here defined as:
MM=TA-2.times.(TA-FA)
[0022] provided that TA-FA<10%. This means that not very much
dimeric or polymeric lactic acid can be present. It is also assumed
that the non-monomeric lactic acid is present in the form of
lactoyl lactic acid (dimer).
[0023] Chiral purity (for an excess (S)-isomer) is here defined
as:
Chiral purity=100%.times.{((S)-isomer)/((R)-isomer+(S)-isomer)}
[0024] The known crystallization techniques can in principle be
applied in the method according to the present invention. An
example of such a technique is melting crystallization (or cooling
crystallization), where the condensed, liquid concentrate or
distillate, which for example contains (S)- or (R)-lactic acid in a
molten state, is directly cooled, so that the (S)- or (R)-lactic
acid crystallizes out. It is preferable to keep the temperature at
which crystallization occurs (the crystallization temperature) as
low as possible, so that the formation of oligomers and polymers of
the .alpha.-hydroxy acid is limited as much as possible. According
to the invention a concentrate is preferably used, since the
preparation of a distillate is unfavourable in terms of process
energy.
[0025] Melting crystallization is a process in which a crystalline
material is obtained from a melt of the material to be
crystallized. This technique is for example described in detail in
Kirk-Othmer, Encyclopedia of Chemical Technology, fourth edition,
Part 7, pages 723-727 (1993), in J. W. Mullin, "Crystallization",
third revised edition, Butterworth-Heinemann Ltd., pages 309-323
(1993) and in J. Ullrich and B. Kallies, Current Topics in Crystal
Growth Research, 1 (1994), which have been recorded here for
reference. The main advantage of melting crystallization relative
to distillation is that much less energy is needed, because the
enthalpy of melting of organic compounds is generally lower than
the enthalpy of evaporation. This advantage also occurs with other
crystallization techniques, because the enthalpy of crystallization
is usually lower than the enthalpy of evaporation. Another
advantage of melting crystallization relative to distillation is
furthermore that the process can generally be carried out at a much
lower temperature--which is advantageous when the organic compound
is thermally unstable.
[0026] The melting crystallization can be carried out with the aid
of a suspension crystallization or a layer crystallization, if
necessary in combination with a washing column or a centrifuge, or
another purification technique. Examples of suitable equipment and
processes are described in Kirk-Othmer, Encyclopedia of Chemical
Technology, fourth edition, Part 7, pages 723-727 (1993), in J. W.
Mullin, "Crystallization", third revised edition,
Butterworth-Heinemann Ltd., pages 309-323 (1993) and J. Ullrich and
B. Kallies, Current Topics in Crystal Growth Research, 1 (1994),
the content of which has been recorded here for reference.
[0027] It has also been found that crystallization of an aqueous
solution gives very good results. In this crystallization treatment
a concentrated lactic acid solution is for example diluted with
water and this is then subjected to one or more cooling and/or
evaporative crystallization steps. In these techniques the
concentrate or distillate is directly cooled (cooling
crystallization) or concentrated by evaporation of water
(evaporative crystallization). The driving force for the
crystallization in the cooling crystallization technique is the
bringing about of supersaturation in the concentrated lactic acid
solution by reducing the temperature of the concentrated lactic
acid solution. As a result of the lower temperature of the solution
the solubility decreases and supersaturation occurs.
[0028] The driving force for the crystallization in the evaporative
crystallization technique is the bringing about of supersaturation
in, for example, a concentrated lactic acid solution by evaporation
of water, for which heat must be supplied in order to keep the
temperature of the concentrated lactic acid solution constant. The
heat of crystallization is thus effectively removed by cooling and
evaporation of water, respectively. Crystallization of the lactic
acid then occurs during the cooling and evaporation of water,
respectively.
[0029] Another highly suitable crystallization technique is
adiabatic crystallization, where the driving force for the
crystallization is the bringing about of supersaturation in, for
example, a concentrated lactic acid solution by evaporation of
water without supplying heat. The evaporation of water has two
effects: (a) the temperature of the concentrated lactic acid
solution becomes lower and (b) the concentration of the acid
increases. Both effects lead to a decrease in the solubility and an
increase in the supersaturation.
[0030] The crystallization steps are preferably carried out
according to the invention by means of adiabatic crystallization or
cooling crystallization, in particular by means of adiabatic
crystallization. Seed crystals are preferably added to feed in the
crystallizations. If a solvent is used in the crystallization, this
is preferably water.
[0031] The .alpha.-hydroxy acid which is crystallized out can then
be separated by the known methods for solid-liquid separation from
the remaining liquid, or mother liquor.
[0032] Examples of suitable separation techniques for separating
the .alpha.-hydroxy acid crystals from the mother liquor are
centrifugation, decanting, filtration, separation by means of one
or more washing columns, or a combination of two or more of these
techniques. In the context of the invention it has been found that
centrifugation and separation with one or more washing columns is
particularly appropriate.
[0033] The mother liquors which are obtained still contain
considerable quantities of .alpha.-hydroxy acid. For optimal
process management it is therefore preferable to feed these mother
liquors back into the process.
[0034] The distillation step is carried out under reduced pressure,
using an .alpha.-hydroxy acid with a total acid content of at least
95% by weight, a monomeric .alpha.-hydroxy acid content of at least
80% by weight and a water content of at most 2% by weight,
calculated in terms of the .alpha.-hydroxy acid. The ratio between
the .alpha.-hydroxy acid enantiomers, if applicable, is preferably
not equal to 1.
[0035] In the distillation according to the invention an
.alpha.-hydroxy acid is formed with a total acid content of at
least 98% by weight, preferably at least 99% by weight, where
.alpha.-hydroxy acid contains at least 95% by weight monomeric
.alpha.-hydroxy acid, calculated in terms of the lactic acid
concentrate, and a distillation residue. The distilled
.alpha.-hydroxy acid preferably contains at least 98.5% by weight
monomeric .alpha.-hydroxy acid. The chiral purity of the
.alpha.-hydroxy acid, if applicable, is preferably 90% or higher,
more preferably 95% or higher, and in particular 99% or higher.
[0036] In the context of the invention "reduced pressure" means a
pressure in the range from 0.1 to 20 mbar, in particular from 0.2
to 10 mbar. The temperature during the distillation under reduced
pressure is preferably 100 to 200.degree. C., in particular 110 to
140.degree. C.
[0037] Impurities with a high boiling point are removed by the
distillation under reduced pressure, because the .alpha.-hydroxy
acid is obtained as the top product. According to the invention
this distillation under reduced pressure is carried out in
particular with the aid of a short-path distiller. The distillation
under reduced pressure can also be carried out at a pressure of 0.1
to 20 mbar, in particular of 2 to 10 mbar, and at a temperature of
100.degree. to 200.degree. C., in particular a temperature of
110.degree. to 140.degree. C., where the .alpha.-hydroxy acid is
preferably brought into the vapour phase by means of film
evaporation, after which the vapour is conveyed to a distillation
column. In this process, separation into two fractions takes place
under reflux, with the top product containing at least 98% by
weight total acid, preferably at least 99% by weight, and the
residue containing residual sugars and polymeric .alpha.-hydroxy
acid. The top product contains at least 95% by weight monomeric
.alpha.-hydroxy acid, calculated in terms of the .alpha.-hydroxy
acid concentrate. The top product preferably contains at least
99.5% by weight monomeric .alpha.-hydroxy acid. The chiral purity
of this top product is preferably 90% or higher, more preferably
95% or higher, and in particular 99% or higher. According to this
preferred embodiment the film evaporation preferably takes place by
means of smeared film evaporation, thin-film evaporation and/or
falling-film evaporation, with the distillation column or columns
having a plate number from 1 to 10. Distillation step (a) ensures
that .alpha.-hydroxy acid is separated from components such as
residual sugars and polymeric .alpha.-hydroxy acid and components
which give a colour to the impure .alpha.-hydroxy acid. These
components or contaminants have a boiling point which is higher
than that of .alpha.-hydroxy acid.
[0038] After isolation, the .alpha.-hydroxy acid which is obtained
by the method according to the present invention is directly
dissolved in a suitable solvent, usually water, in order to prevent
coagulation of the hygroscopic .alpha.-hydroxy acid occurring. The
concentration of the .alpha.-hydroxy acid solution so obtained can
in principle have any desired concentration. In practice this will
usually vary from 30 to 95%. Concentrations commonly occurring on
the market are 80-90%.
[0039] The invention also relates to an .alpha.-hydroxy acid or an
.alpha.-hydroxy acid solution with a chiral purity of at least 99%
and a colour of not more than 10 APHA units, with the
.alpha.-hydroxy acid or the .alpha.-hydroxy acid solution having an
acceptable odour, in particular for pharmaceutical applications. In
the case of an .alpha.-hydroxy acid solution the solvent is
preferably water. The chiral purity is preferably at least 99%, in
particular at least 99.5%, which corresponds to 99% enantiomeric
excess (ee) or higher. Most preferable is chiral .alpha.-hydroxy
acid, or the solution thereof, whose chiral purity is at least
99.8% (i.e. at least 99.6% ee).
[0040] The .alpha.-hydroxy acid or the .alpha.-hydroxy acid
solution also meets the following requirements:
[0041] alcohol content: not more than 250 ppm (alcohol is methanol,
ethanol or other alcohol, as alcohol as such or in the form of a
lactate).
[0042] total nitrogen: not more than 5 ppm.
[0043] total sugar: not more than 100 ppm.
[0044] total polysaccharides: not more than 100 ppm.
[0045] organic acids (other than lactic acid): not more than 250
ppm.
[0046] With regard to odour the .alpha.-hydroxy acid or the
.alpha.-hydroxy acid solution possesses a considerable improvement
for application in foods and a higher chemical purity than the
products according to the prior art.
[0047] When it is chiral, the .alpha.-hydroxy acid according to the
invention can be both an S-.alpha.-hydroxy acid and an
(R)-.alpha.-hydroxy acid, depending on the microorganism which is
used in the fermentation.
[0048] Because of their high chiral purity both the
(S)-.alpha.-hydroxy acid and the (R)-.alpha.-hydroxy acid or the
solutions thereof can very suitably be applied for chiral
syntheses. The chirally pure (S)-.alpha.-hydroxy acid or solutions
thereof are also very suitable for being applied in pharmaceutical
preparations.
[0049] The invention therefore also relates to a pharmaceutical
preparation which contains the (S)-.alpha.-hydroxy acid or the
(S)-.alpha.-hydroxy acid solution described above. The invention is
now illustrated by means of the following example.
EXAMPLE
[0050] (S)-lactic acid with the following properties is used as the
starting material:
1 Total acid content 95.4% Free acid content 91.1% Colour (fresh)
4850 APHA Total nitrogen 1080 ppm Total residual sugars 6490 ppm
Chiral purity 99.61%
[0051] In a first crystallization step a double-walled 2.7-litre
vessel was connected with a thermostat bath and 2045 g of the
starting material described above was put into the vessel. The acid
was cooled to 40.degree. C. while stirring and inoculated with 0.4
g of a suspension which contained seed crystals. The acid was then
cooled from 40.degree. to 30.degree. C. in 5 hours in accordance
with a linear cooling programme. The crystals formed were
rod-shaped and many small particles were formed. After 5 hours the
temperature of the thermostat bath was 30.degree. C. and that of
the crystal suspension of the acid was 31.9.degree. C. The
suspension was centrifuged (Sieva laboratory centrifuge, Hermle).
831 g of crystals and 1061 g of mother liquor were obtained (yield
of 46%, calculated in terms of lactic acid). Some of the crystals
from the crystallization were dissolved in water (90% solution) and
the solution was analysed. The results are shown in the table
below.
2 Crystallization Colour (fresh) 349 APHA Colour (after hearing)
713 APHA Total nitrogen 55 ppm Total polysaccharides 473 ppm Total
residual sugars 430 ppm Chiral purity 99.97%
[0052] An amount of 125 g of the crystals obtained above was melted
in a microwave oven and the liquid was put into a short-path
distiller (KDL-4). The conditions were as follows: oil bath
temperature 120.degree. C., feed rate 15 ml/min, pressure about 1
mbar, rotor speed 250 r.p.m., the cooling water was tap water.
[0053] 94.4 g of distillate and 13.3 g of residue were obtained.
The distillate was diluted with water until a 90% solution was
obtained and this solution was analysed for colour. Colour (fresh):
6 APHA. Colour (after heating): 5 APHA.
* * * * *